The ultimate goal of the proposed research is to determine the role of plasma lipoproteins in the extracellular accumulation of lipids in the arteries and aorta. We wish to focus on the various physicochemical and enzymatic factors influencing the retention of lipoproteins in the arterial tissues and the subsequent accumulation of lipid, utilizing model systems. Therefore, our efforts will be directed toward clarification of a) the interactions of plasma lipoproteins with aortic connective tissue components, such as glycosaminoglycans, proteoglycans, elastin, and collagen and b) the effects, on these interactions, of the changes occurring in the surface and interior properties of the lipoproteins during their circulation and after their entry into the aorta. With respect to the lipoprotein modifications during the circulation, we will study the effects of lecithin-cholesterol acyltransferase and lipoprotein lipase, placing emphasis on the former. With respect to the modifications of lipoproteins in the aorta after entry, the effects of lysosomal, proteolytic, lipolytic, and other enzymes will be determined. Human plasma lipoproteins will mainly be used for the interaction and modification studies. Swine aortic tissue will serve primarily as a source of connective tissue components and of various enzymes, due to the limited availability of human tissues for systematic studies and to the close similarity between human and swine atherosclerosis. We hope to show that lipid accumulation in atherosclerosis is manifested by changes in the physical state of lipoproteins and lipids and in their macro- and microenvironments.